Transcriptional and translational dual regulated oncolytic herpes simplex virus vectors
AssigneesVirogin Biotech (Shanghai) Ltd, Virogin Biotech Canada Ltd
InventorsWilliam Wei-Guo Jia, Jun Ding, Guoyu Liu, Xiaohu Liu, Dmitry V. Chouljenko
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Abstract
An HSV vector with ICP27 under control of CXCR4 promoter and ICP34.5 under control of miRNA-124/143, wherein the vector has a deletion of one RL and one RS region of the viral genome. Within optional embodiments the mutation is a deletion containing the second copy of the ICP34.5 gene. These constructs provide increased safety without sacrificing efficacy. The HSV vector also incorporates a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CMV promoter.
Claims25
A recombinant herpes simplex virus comprising a modified oncolytic herpes virus genome, wherein the modified herpes virus genome comprises at least one miRNA target sequence operably linked to a first copy of an ICP34.5 gene, and a second copy of the ICP34.5 gene comprises an inactivating mutation, and further comprising replacing an ICP47 promoter with an immediate early gene promoter such as an ICP4, ICP0, or, ICP27 regulatory sequence operably linked to an ICP47 gene, and wherein the ICP47 gene comprises an inactivating deletion in the natural ICP47 regulatory sequence. Within further embodiments, the immediate early gene promoter may be selected from either HSV-1 or HSV-2.
Dependencies are inferred from the claim text.